Thromboembolism is an important cause of morbidity and mortality. It occurs when a blood clot breaks free and is carried by the blood stream to obstruct a blood vessel at another site. Thromboembolic disease includes venous thromboembolism, for example deep vein thrombosis or pulmonary embolism, arterial thrombosis, stroke and myocardial infarction.
Thromboembolic diseases may be treated using anticoagulants. One approach has been to target the inhibition of factor XIa (FXIa). Factor XIa is a plasma serine protease involved in the regulation of blood coagulation. Factor XIa is an activated form of factor XI, which is activated by factor XIIa, thrombin, and it is also autocatalytic. FXIa is a member of the “contact pathway” and activates factor IX by selectively cleaving Arg-Ala and Arg-Val peptide bonds. Factor IXa, in turn, activates factor X. The safety of this target is supported by the observations that FXI deficiency in humans (hemophilia C) results in a mild bleeding disorder. In addition to this, the efficacy and side effects of this target have been shown using experimental thrombosis and bleeding models in mice lacking FXI, and in baboons and rabbits treated with anti-FXI neutralizing antibodies. These results suggest that FXIa inhibitors will show a potent anti-thrombotic effect without bleeding. Therefore, factor XIa is an attractive target for anti-thrombotic therapy without any bleeding side effect.
It has been described in Patent literature 1 that compounds of formula (A):

wherein AA represents a 5- to 12-membered heterocycle, etc.; L1A represents —CH═CH—, etc.; R11A represents benzyl, etc.; MA represents imidazolyl, etc; are useful as selective inhibitors of factor XIa or dual inhibitors of FXIa and plasma kallikrein.
Furthermore, it has been described in Patent literature 2 that a compound of formula (B-I):

wherein AB represents a 5- to 12-membered heterocycle, etc.; L1B represents —CH═CH—, etc.; R11B represents benzyl, etc.; R3B represents phenyl, etc.; R4B represents chlorine, etc.; R8aB represents hydrogen, etc; or formula (B-II):

wherein MB represents pyridyl, etc.; and the other symbols have the same meanings as described above; inhibit factor XIa and/or plasma kallikrein.
Furthermore, it has been described in Patent literature 3 that compounds of formula (C):

wherein WC represents CO, etc.; GC represents a direct bond, etc.; G1C, G2C, G3C and G4C each independently represents C or N, etc.; R9C represents aryl, etc.; R10C represents heteroaryl, etc.; R1AC represents heteroarylalkyl, etc.; are useful as gamma secretase modulators, however, it is not reported that the compound represented by formula (C) has factor XIa inhibitory activity.
Furthermore, it has been described in Patent literature 4 that compounds of formula (D):

wherein R1D represents hydrogen, etc.; R2D represents aryl, etc.; R3D represents hydrogen, etc.; R4D represents hydrogen, etc.; R5D represents heteroarylalkyl, etc.; is useful as p38 MAP kinase modulator.
Furthermore, it has been described in Patent literature 5 that compounds of formula (E):

wherein LE represents a linker providing 0-6 atoms, etc.; XE represents heteroaryl, etc.; ZE represents halogen, etc.; QE represents CO, etc.; R2E and R3E each independently represents hydrogen, aryl, etc.; are useful as dipeptidyl peptidase inhibitors.
[Patent literature 1] WO2007070826
[Patent literature 2] WO2008076805
[Patent literature 3] WO2009076337
[Patent literature 4] WO2003068230
[Patent literature 5] EP1506967A1